A. Specific Aims. Two fundamental processes often encountered in the synthesis of complex natural products are: 1) the (direct) creation of a chiral center or centers on a chiral substrate, and 2) the coupling of two chiral fragments with concommitant creation of chiral centers. These tasks can, in principle, be achieved with high stereoselection by the use of a chiral external reagent. The reaction involving a chiral reagent provides the product which does or does not contain the chiral moiety of the reagent. If it does, the reagent is called "internal", and if not, "external". In order to demonstrate this principle and achieve a higher level of stereochemical control, we plan to proceed through three stages. The first stage is concerned with the design of boranes of C2 symmetry, e.g., homochiral trans-2,5-dimethylborolane, and examination of these reagents in terms of single and multiple asymmetric induction. The reactions to be investigated include: hydroboration, nucleophic carbonyl addition, the aldol reaction, ketone reduction, and the Diels-Alder reaction. This borane work will be followed by similar studies on silanes and stannanes. The second phase is aimed at elucidating the behavior of a metal cation which may chelate with either one or both of the alkoxyl substituents attached to two reactants, e.g., a pair of an enolate and an aldehyde in an aldol reaction. The metal cation chelation is a complicated process and its detailed information will provide a synthetic tactic complimentary to that using a chiral external reagent. Finally the knowledge that will accrue through the pursuit of stages 1 and 2 will be utilized to modify several major steps of the recorded monensin and rifamycin S syntheses and to execute the proposed erythronolide A synthesis. The new versions of these syntheses will hopefully disclose our attempts to enter a next generation of polyketide synthesis. Monensin, rifamycin S, and erythromycin A are well-known for their significant antibiotic activities.